New molecules in malaria sporozoite-hepatocyte infection

超出所提供的空间。在感染最后的肝细胞之前，疟原虫孢子在宿主体内的几个细胞中迁移。我们的初步研究表明，这种迁移对疟疾的建立至关重要，因为；(1)激活孢子子，使其能够抵抗肝细胞的侵袭；（ii）激活邻近的肝细胞，使其易受孢子虫感染。我们计划确定寄生虫和宿主细胞机制和分子参与这两个关键方面的感染。在通过宿主细胞的迁移过程中，孢子接触肝细胞的细胞质。这触发了肝细胞感染所需要的孢子胞吐作用。使用肝细胞提取物，我们将确定激活孢子体感染的分子和这些分子在孢子体中识别的受体。我们还将研究这种激活级联导致胞吐的信号转导机制。（ii）通过宿主肝细胞的迁移诱导肝细胞生长因子（HGF）的释放，使肝细胞易受疟原虫感染。我们将研究hgf介导的肝细胞对感染易感性的潜在机制，包括细胞骨架重排、寄生物液泡酸化、胆固醇需求和肝细胞凋亡抑制。这项研究的结果将有助于了解介导疟疾在宿主体内发展的第一步——肝细胞感染的分子和细胞机制。感染所需的新型疟原虫和肝细胞因子的表征具有作为疾病控制新靶点的重大潜力。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. Plasmodium sporozoites migrate through several cells in the host before infecting a final hepatocyte. Our Preliminary Studies show that this migration is essential for the establishment of malaria because; (i) it activates sporozoites making them competent for hepatocyte invasion; (ii) it activates neighboring hepatocytes making them susceptible for sporozoite infection. We plan to identify parasite and host cell mechanisms and molecules involved in these two crucial aspects of infection. (i) During migration through host cells sporozoites contact the cytosol of hepatocytes.This triggers exocytosis in sporozoites that is required for infection of hepatocytes. Using hepatocyte extracts we will identify the molecules that activate sporozoites for infection and the receptors that these molecules recognize in the sporozoite. We will also study the mechanism of signal transduction of this activatory cascade resulting in exocytosis. (ii) Migration through host hepatocytes induces the release of hepatocyte growth factor (HGF) that makes hepatocytes susceptible for Plasmodium infection. We will investigate the mechanisms underlying HGF-mediated hepatocyte susceptibility for infection, including cytoskeletal rearrangements, acidification of the parasitophorous vacuole, cholesterol requirement, and hepatocyte apoptosis inhibition. Results from this study will contribute to the understanding of the molecular and cellular mechanisms mediating the first step of malaria development in the host: the infection of hepatocytes. The characterization of novel Plasmodium and hepatocyte factors that are required for infection hold significant potential as novel targets for disease control. PERFORMANCE SITE ========================================Section End===========================================